Evaluation of the Efficacy of N-Succinimidyl 4-[F]fluorobenzoate ([F]SFB) as a Synthon for Labeling Peptides, Illustrated by the Reaction with Glutathione

The conjugation of N-succinimidyl-4-[F]fluorobenzoate ([F]SFB), a widely used radiosynthon for labeling biologically complex molecules for use as radiopharmaceuticals (RPs) in positron emission tomography (PET), with a model tripeptide, glutathione (GSH), was studied. [F]SFB was prepared using the previously developed method of direct copper(II)-mediated radiofluorination of arylpinacolboronate as a labeling precursor. The efficiency of the conjugation of [F]SFB, which was recovered from the reaction mixture by solid-phase extraction (SPE) on disposable cartridges, with GSH in an acetonitrile/phosphate buffered mixture with pH 8.4 depended on the ratio of the aqueous and nonaqueous phases and the peptide concentration. With equal volumes of the components (0.5 mL) and a GSH concentration of 1.0 mg/mL, the conjugation yield of 97% was achieved. This serves as further evidence of the efficiency of SPE purification, which removes chemical impurities that could otherwise compete in the conjugation reaction. This purification method using disposable cartridges can be easily adapted to any automated modules, including cassette ones. This contributes to the more effective use of [F]SFB in synthesizing radiopharmaceuticals based on complex biomolecules.